Page 17 - TD-4-2

Tumor Discovery Melanoma exosomes in metastasis

Table 1. Melanoma‑derived exosomes as therapeutic targets
Target Function and role in exosomes Therapeutic potential References
CEMIP Enhances exosome-mediated tumor invasion and Inhibiting CEMIP reduces metastasis potential 22
metastasis
Rab27a/b Regulates exosome secretion and cargo release Rab inhibitors can block tumor exosome release 75
Syntenin-1 Facilitates sorting of tumor-promoting proteins Suppressing syntenin-1 reduces exosomal 76
into exosomes pro-metastatic factors
HSP90 Involved in the exosomal transport of oncogenic HSP90 inhibitors block exosomal stress responses 77
signaling proteins
Tetraspanins (CD9, Regulate exosome biogenesis and uptake in Potential for exosome-based drug delivery 78
CD63, CD81) recipient cells modifications
Alix Controls ESCRT-mediated exosome formation Alix inhibitors could disrupt melanoma exosome 79
secretion
Integrins (ITGαvβ3, Direct exosomes to specific metastatic sites Targeting integrins can block organotropic 82
ITGα6β4) metastasis
PD-L1 Delivered by tumor exosomes to suppress immune Anti-PD-L1 therapy enhances anti-tumor 67
response immunity
MicroRNAs (miR-155, Modulate tumor progression and immune evasion Blocking oncogenic miRNAs may reduce 83
miR-211) via exosomes melanoma progression
HSP70 Promotes exosome-mediated stress adaptation HSP70 inhibitors may impair tumor exosome 81
function
Abbreviations: CD: Cluster of differentiation; CEMIP: Cell migration-inducing and hyaluronan-binding protein; ESCRT: Endosomal sorting complexes
required for transport; HSP: Heat-shock protein; PD-L1: Programmed death-ligand 1.

to be optimized for clinical use to ensure both purity and 5.4. Emerging exosome-based therapeutic
consistency. Moreover, immunogenicity poses another strategies
challenge, as exosomes derived from non-autologous Recent advances have highlighted the therapeutic potential
sources may trigger immune responses in the recipient, of engineered exosomes as both therapeutic agents and
reducing their therapeutic efficacy. The long-term safety delivery systems for various diseases, including melanoma.
profile of exosome-based therapies is still not fully Through genetic modification, surface engineering,
understood, requiring extensive research and clinical and cargo loading, exosomes can be tailored to enhance
trials to assess potential risks. Furthermore, the lack of targeting ability, improve drug delivery efficiency, and
standardized protocols for exosome preparation, isolation, reduce systemic toxicity. By modifying exosomal
84
and characterization complicates the consistency of clinical membranes or incorporating bioactive molecules,
outcomes. Clear regulatory guidelines are needed to researchers aim to refine their specificity and therapeutic
ensure the safety and efficacy of exosome-based therapies efficacy while minimizing off-target effects. 85
in clinical settings.
One promising approach involves modifying exosome
Efficient targeted delivery of exosomes remains a
critical challenge in maximizing therapeutic benefits. cargo to enhance cancer immunotherapy. Tumor-derived
While exosomes hold promise for targeted delivery of exosomes carrying tumor-associated antigens can
therapeutic agents, their ability to reliably reach specific stimulate antigen-presenting cells, thereby strengthening
tissues or cells is often inconsistent. Developing strategies the anti-tumor immune response. In addition, engineered
to enhance the specificity of exosome targeting is crucial exosomes depleted of PD-L1, a key immune checkpoint
for improving treatment outcomes and minimizing off- regulator, have been explored to enhance the effectiveness
86
target effects. Advances in surface modification techniques, of PD-1/PD-L1 inhibitors in melanoma therapy.
such as functionalizing exosomes with targeting ligands, These findings indicate that engineered exosomes may
are required to improve their specificity and efficacy. complement current immunotherapies.
Targeting specific cell types or tissues with exosomes will In the context of chemotherapy, exosomes have been
be key to overcoming current limitations and ensuring modified to serve as drug carriers, improving the delivery
that exosome-based therapies achieve their full therapeutic of cytotoxic agents such as paclitaxel, doxorubicin, and
potential. cisplatin. Compared to synthetic nanoparticles, exosomes
87

Volume 4 Issue 2 (2025) 9 doi: 10.36922/td.7108